Maternal helminth infection: Immunological and developmental consequences for the offspring

• Applicant: Professorin Dr. Clarissa Prazeres da Costa
• Subject Area: Pneumology, Thoracic Surgery ; Immunology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 254868190

An extraordinary attribute of helminths, such as schistosomes, is their capability to constantly modulate their hosts immune system in order to guarantee their own survival. Immune responses against the helminth are potentially host-destructive and therefore need to be tightly controlled by a variety of mechanisms. Interestingly, this control is not limited to the helminth itself but expands to unrelated antigens such as allergens and we have shown previously in a model of allergic airway inflammation that schistosome infected mice are protected from disease partially by expanding Treg cells. A completely new question in this field of Hygiene- Hypothesis-related research that we started to address recently is, whether the profound immunological effects of this chronic, non-transplacental infection expand to the next generation. Offsprings generated by mating of infected females during the three consecutive and distinct immune phases elicited during the course infection were either partially or almost completely protected from allergic airway inflammation or showed aggravation of the disease. During these different phases of infection the offsprings allergy susceptibility was reflected in distinct placental gene expression, cytokine environment and the offsprings early immune cell composition. Moreover, we identified that maternal-derived Interferon-gamma during the acute phase of infection is an essential element for the progenys protective immune phenotype. Inheritance of these schistosome-induced effects through the germline could be excluded. Taken together, we hypothesize that schistosome-induced immune responses in the mother change the placental environment which epigenetically affects the development of the hematopoietic system and thereby shapes the offsprings susceptibility to allergies and infections. The main objectives within this proposal are to investigate in detail the impact of the three immune phases on the development of the offsprings immune system, starting from alterations at the gametic and embryonic stage to investigation of the allergic airway inflammation phenotype in aged offspring and the F2 generation. We thereby aim to aid our understanding of how our immune system evolved under evolutionary helminthic pressure and how this contributes to the epidemiological findings of low allergy rates in third world countries.

• DFG Programme: Research Grants